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IMMUNE, DERMAL AND INFECTIOUS DISEASES

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Immune Diseases

Activities: NIOSH Research Projects

Identification of Occupational Allergens

Exposures to substances that can cause inflammatory or immune reactions are important hazards in certain work environments and important causes of occupational lung diseases such as asthma and allergic alveolitis. This project is intended to develop improved techniques to detect such immune reactions before adverse clinical outcomes occur. The project will involve the analyses of clinical samples, environmental bulk samples, and environmental aerosol samples. Successful completion of these investigations should lead to the development of effective prevention strategies for occupational allergies and asthma.

Project contact: Don Beezhold
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 1998-2012

Immunochemical Biomonitoring for Worker Exposure and Disease

This continuing project, Immunochemical Biomonitoring for Worker Exposure and Disease, supports multiple branch projects through; the management/planning of field sample collection; development of new classical and immunochemical biomonitoring methods; and validation/adaptation of existing methods. Immunochemical Biomonitoring for Worker Exposure and Disease, a continuing project, is evaluating industrial and agricultural chemicals with known acute and chronic toxicities, which present a significant exposure risk for workers. Biological monitoring can assess exposure by analyzing acute and latent metabolites in various biological media. The goal of this project is to develop low-cost, rapid immunochemical and analytical chemistry biomonitoring methods that will be used to identify exposures and evaluate potential interventions. Concurrent with development of exposure assessment methods, this project will identify and develop new multiplex immunochemical methods to evaluate biomarkers of occupational illness or subclinical signs of occupational illness. Biological monitoring, through the validation and development of new methods, is a powerful tool for reducing risk and creating safer work practices.

Project contact: Cynthia Striley
Division of Applied Research and Technology, Biomonitoring and Health Assessment Branch
(513) 533-8462
Project period: 2004-2014

Validation Studies in Occupational Immunotoxicology

Validation Studies in Occupational Immunotoxicology, a continuing, multifaceted project, is addressing the development of occupational asthma and other immunotoxic diseases in numerous industries. Current efforts are focusing on enhancing diagnostic capabilities for occupational hypersensitivity and autoimmune diseases using 3rd generation immunoassays or multiplexed autoantibody analysis for workers exposed to numerous allergens (latex proteins, flour and wheat in the baking industry, as well as other occupational allergens (fel d1), autoimmune toxicants and bioterror agents. This work will address needs in Manufacturing and Health Care and Social Assistance Sectors and is associated with Emergency Preparedness and Response, Immune and Dermal Diseases, Respiratory Disease, and Exposure Assessment Cross-Sectors.

Project contact: Raymond Biagini
Division of Applied Research and Technology, Biomonitoring and Health Assessment Branch
(513) 533-8462
Project period: 1999-2011

BHAB Research Development and Planning

BHAB Research Development and Planning (Biology/Chemistry), a continuing project, provides scientific and administrative oversight for the Biomonitoring and Health Assessment Branch (BHAB) investigative research, methods development and collaborations in biological monitoring and biomarkers, reproductive health assessments, genotoxicity, genetics and immunochemistry and immunotoxicology. The scientific management provided ensures BHAB research activities are relevant to NIOSH goals, timely, and scientifically and fiscally sound. Project outputs include biomarkers of exposure, effect of exposure, susceptibility to exposure, new research methods, reproductive health assessments, and journal publications, which are shared with internal and external partners. Work crosses all sectors but primarily occurs in Healthcare and Social Assistance, Construction and Services.

Project contact: Debra Debord
Division of Applied Research and Technology, Biomonitoring and Health Assessment Branch
(513) 533-8462
Project period: 1980-2014

Orthophthalaldehyde (OPA) Hazard Assess

This project will assess occupational exposures to OPA and determine if healthcare workers are experiencing adverse effects associated with exposure. To assess exposure, this study will also develop analytical methods for environmental monitoring of OPA and determine the feasibility of an OPA biomarker. Because of the absence of published toxicological data on OPA, testing will be conducted in experimental animals. The toxicological testing will focus on dermal and respiratory irritation and sensitization. Dose-response data will be obtained for hazard identification risk assessment, which, along with health assessments, will serve as the basis for establishing exposure limits.

Project contact: Mark Toraason
Division of Applied Research and Technology, Biomonitoring and Health Assessment Branch
(513) 533-8462
Project period: 2009-2011

UV Native Fluorescence Based Monitor for Workplace Exposures

The purpose of this new project, UV Native Fluorescence Based Monitor for Workplace Exposures, is to develop and evaluate a readily adaptable, next generation, direct reading, personal monitor (DRPM) for use in measuring worker exposure to a wide variety of chemicals. This research addresses the NIOSH direct-reading initiative Research Need #6 by partnering with other organizations to seek new uses of existing direct-reading technology and Research Need #2 by development of new or refined technologies. Project activities address goals in the Transportation, Warehouse & Utilities and the Construction Sectors and the Exposure Assessment Cross-Sector. The development of DRPM for volatile and semi-volatile workplace chemicals will be helpful in rapidly assessing chemical exposure and will result in more realistic occupational exposure assessments and allow for rapid interventions leading to reduced worker exposures and thus preventing occupational illness and disease.

Project contact: John Snawder
Division of Applied Research and Technology, Biomonitoring and Health Assessment Branch
(513) 533-8462
Project period: 2009-2010

Isocyanate Method Development and Exposure Assessment

The purposes of this project are 1) to continue to investigate problematic issues in isocyanate sampling and analysis, 2) to develop and evaluate a novel total isocyanate method, 3) to continue technology transfer efforts through collaboration with commercial laboratories, other researchers, and participation in ISO, 4) to contribute to reduction of isocyanate exposures in the truck bedlining industry, 5) to contribute to the investigation of the relationship between isocyanate exposure and health effects in TDI manufacturing facilities, and 6) to assist in the accurate measurement of community TDI exposures and 7) as a member of the Spray Foam Insulation Working Group created by the EPA to help direct future research in this arena. Expected intermediate outcomes and outcomes include 1) technology transfer through collaborations, patents, and ISO involvement, 2) reductions in isocyanate exposures in the truck bedlining industry, 3) a better understanding of the relationship between TDI exposure and health effects, and 4) better understanding of issues facing the spray foam insulation industry .

Project contact: M Kathleen Ernst
Division of Applied Research and Technology, Chemical Exposure and Monitoring Branch
(513) 533-8462
Project period: 2004-2010

Educational Materials on Staph/MRSA for Corrections Workers (PHP)

The purpose of this project is to develop and disseminate one or more educational products (e.g., fact sheets, Workplace Solutions, brochures, and/or posters) for the prevention of exposures to methicillin-resistant Staphylococcus aureus (MRSA) in corrections facilities. These will be targeted at corrections staff, who are at greatest risk of MRSA exposure. Given the possibility of inmate to employee transmission, a poster or fact sheet (in English and Spanish) targeted at inmates may be included.

Project contact: Winifred Boal
Division of Surveillance, Hazard Evaluations and Field Studies, Surveillance Branch
(513) 841-4428
Project period: -2012

Emerging Issues in Bloodborne Pathogens

This project supports research on emerging issues in occupational transmission of bloodborne pathogens among healthcare workers, within the United States of America and abroad. This project includes: 1) Dissemination and implementation of the Joint OSHA NIOSH Safety and Health Information Bulletin; 2) Review paper describing the hazards and risks in the operating room, associated health effects, and directions for future research; 3) review and update of current domestic and foreign recommendations for functionality, accessibility, visibility and accommodation of sharps containers; and 4) supports the WHO efforts to promote prevention of occupational transmission of bloodborne pathogens among HCWs in international settings due to needlestick injuries which include: Africa, Asia, and Latin America.

Project contact: Ahmed Gomaa
Division of Surveillance, Hazard Evaluations and Field Studies, Surveillance Branch
(513) 841-4428
Project period: 2002-2010

Emerging Issues in Bloodborne Pathogens

This project supports research on emerging issues in occupational transmission of bloodborne pathogens among healthcare workers, within the United States of America and abroad. This project includes: 1) Dissemination and implementation of the Joint OSHA NIOSH Safety and Health Information Bulletin; 2) Review paper describing the hazards and risks in the operating room, associated health effects, and directions for future research; 3) review and update of current domestic and foreign recommendations for functionality, accessibility, visibility and accommodation of sharps containers; and 4) supports the WHO efforts to promote prevention of occupational transmission of bloodborne pathogens among HCWs in international settings due to needlestick injuries which include: Africa, Asia, and Latin America.

Project contact: Ahmed Gomaa
Division of Surveillance, Hazard Evaluations and Field Studies, Surveillance Branch
(513) 841-4428
Project period: 2002-2010

Statistical Methods Development and Application

This project provides the resources for independent research on statistical methods. New statistical methodologies will be developed and the project will provide support for initial studies that are deemed significant to future research. Current activities supported by this project are the statistical analysis methods involved in real time polymerase chain reaction (PCR) technology, genetic microarrays, proteomics, classification methods, parameterization of nonlinear biological responses, analysis of heart rate variability data, parameterization and analysis of actigraphy data, and modeling nonlinear biological response functions are current activities supported by this project. The creation and implementation of appropriate statistical methods and study designs will allow researchers to better interpret data and, therefore, allow information and knowledge gained through research to be more effective in preventing death and injury among the US workforce.

Project contact: Michael Andrews
Health Effects Laboratory Division
(304) 285-6121
Project period: 1999-2014

Development of new immunodiagnostic and detection techniques for indoor fungi

The goal of this project will be to identify major allergens of Paecilomyces variotii and produce species-specific monoclonal antibodies towards these allergens. Paecilomyces variotii is a cosmopolitan filamentous fungus that is ubiquitous in indoor and occupational environments throughout the United States. Paecilomyces inhabits the soil, decaying plants or foods and its spores can grow and contaminate damp indoor environments. Exposure to fungal spores and fragments of this species can be as extremely high in occupational environments and has been shown to be a risk factor for a number of allergic and invasive diseases. In this project we will attempt to address the problems associated with measuring personal exposure to this fungus in occupational settings by identifying the major allergens and produce species-specific monoclonal antibodies towards these allergens. These diagnostic reagents will then be utilized to create practical immunoassays for the detection of this fungus in clinical and environmental samples. This project should result in peer reviewed journal articles which will provide scientific data regarding the mechanism of immune sensitization to fungi found in the workplace. The knowledge gained from this study will address specific NIOSH research goals for reducing occupational causes or contributing factors to acute and chronic illness and disease in agricultural workers and respiratory conditions and diseases in the manufacturing sector.

Project contact: Don Beezhold
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2006-2010

Cutaneous Bioactivation of Xenobiotics: Hapten vs. Prohapten

The purpose of this project is to develop an in vivo model of allergic skin sensitization that can discriminate between chemicals requiring metabolic activation for sensitization (prohaptens) and those that can sensitize without biological activation (haptens). The model will involve the dermal application of various pharmacological inhibitors of the cytochrome p 450 pathway prior to performing either the local lymph node assay (LLNA) or/and mouse ear swelling test (MEST). Selective inhibition of the cytochrome P450 (CYP) pathway should distinguish between direct acting haptens and metabolically activated pro-haptens. Validation of the models will be done using known direct acting haptens and pro-haptens. Successful development of these models will produce data that strengthens in silico hazard predictive models and allows for substitution or modification of allergenic chemicals and drugs. This project will contribute to the immune cross-sector goal to advance knowledge regarding the impact of occupational exposures to chemicals or biological agents.

Project contact: Paul Siegel
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2007-2010

Configurational Entropy in Receptor-Ligand Binding: The MIE-NN Method

An accurate and tractable method to calculate how toxic molecules, or ligands, bind to biological receptors on large molecules such as proteins has been identified. This development has implications in accurately screening chemicals for toxicity. Further development of the method, called MIE-NN, will furnish the first reliable calculation of entropy costs when ligands bind to receptors. This project will examine the validity of the MIE-NN method for more complex systems, and study chemical systems of occupational interest. One such chemical is a nanoparticle utilized in industry with a cup like structure that captures smaller molecules such as benzene. This nanoparticle is a valid receptor-ligand system, and consistent with mission interests of toxicities emerging from nanotechnology. The second system is the estrogen receptor, which is implicated in a number of toxicological mechanisms.

Project contact: Vladimir Hnizdo
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2008-2010

Airway Fungal Exposure and Allergic Sensitization in Mice

The goal of the proposed research will be to compare the immunological health effects of lung exposure to fungal spores or to hyphal fragment preparations. Agriculture as well as construction and remediation workers are exposed to elevated levels of fungi and can experience rhinitis, respiratory allergic symptoms and/or asthma as a result of their exposure. This project will have two major areas of study; 1) Determination of the health effects following aspiration of hyphal fragments from Stachybotrys chartarum and Alternaria alternata in the absence of intact spores in mice, and 2) Comparison of the ability of aspirated spores or hyphal suspensions from Aspergillus spp, S. chartarum, and A. alternata to exacerbate respiratory allergy to ovalbumin. This project should result in peer reviewed journal articles which will provide scientific data regarding the mechanism of immune sensitization to fungi found in the workplace. The knowledge gained from this study will address specific NIOSH research goals for reducing occupational causes or contributing factors to acute and chronic illness and disease in agricultural workers and respiratory conditions and diseases in the manufacturing sector.

Project contact: Steven Templeton
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2009-2012

Characterization of toluene diisocyanate exposure biomarkers

The overall goal of the proposed project is to isolate and characterize specific proteins that react with isocyanates when exposed to occupationally-relevant levels of TDI. Diisocyanates are highly reactive chemicals used in production of polyurethane products that represent a significant occupational exposure hazard to workers. This project seeks to reduce isocyanate-induced respiratory disease by developing improved detection methods for isocyanate exposure and characterizing the chemical changes to proteins that cause isocyanate-induced disease. Experiments are proposed that will result in the identification of specific biomarkers of TDI exposure and better reagents for identification of dNCO sensitized workers (e.g. appropriate hapten-protein conjugate to screen workers for TDI-specific antibodies). This project should result in peer reviewed journal articles which will provide scientific data regarding the mechanism of haptenation by isocyanates. The knowledge gained from this study will address specific NIOSH research goals for reducing respiratory disease and occupational skin disease in the manufacturing and service sectors.

Project contact: Justin Hettick
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2009-2012

Evaluation of Perfluoralkyl acids (PFAAs) immunotoxicity

The purpose of this project is to evaluate the immunotoxic effects associated with PFAAs exposures. PFAAs are synthetic chemical substances whose unique chemical properties, such as high stabilities and extremely low surface tensions, lend them to be valuable in a wide range of consumer and industrial applications. Exposure to one specific PFAA, PFOA, although no longer used in manufacturing, but still persistent in the environment, has been shown in a murine model to be both immunosuppressive and to have a potential role in asthma and allergy. Studies investigating the mechanisms underlying the immune modulation mediated by exposure to PFOA are limited. Due to the potential health effects linked to PFOA exposure, replacement PFAAs are now being used in the manufacturing process. Little is known about what effects of these compounds will have on immune function. The overall goal of this project is to evaluate the immunotoxic effects associated with individual PFAAs that are still used in the manufacturing process, and to investigate the mechanism mediating the identified immunological alterations associated with PFOA exposure. This project should result in peer reviewed journal articles which will provide scientific data regarding the immunotoxic effect of PFAAs. The knowledge gained from this study will address specific NIOSH research goals for reducing respiratory disease and occupational skin disease and hazard identification of occupational chemicals/allergens.

Project contact: Jennifer Franko
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2009-2012

Immunotoxicological evaluation of occupational chemicals

The overall objective of this project is to identify occupational and environmental chemical hazards and evaluate immune function and mechanism associated with exposure. The Immunotoxicology and Hazard Identification Lab will achieve this goal through both individual projects and collaborations. This research will contribute to increased identification of immunological hazards encountered in the workplace. Further evaluation of these compounds will allow for better risk assessment which will ultimately establish occupational exposure limits. Expansions of the immunological database for human exposure to chemicals in the workplace and the development and publication of NIOSH guidance documents and materials will help to educate workers and the general public. This project should result in peer reviewed journal articles which will provide scientific data regarding the immunotoxic effect of chemical exposures. The knowledge gained from this study will address specific NIOSH research goals for reducing respiratory disease and occupational skin disease and hazard identification of occupational chemicals/allergens.

Project contact: Stacey Anderson
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2009-2012

Factors influencing the transmission of influenza

The goal of this project is to better understand transmission of the influenza virus. One of the most important factors governing the airborne transmission of any disease is the amount of airborne infectious material that is present in the environment where uninfected individuals could potentially inhale it. This project is designed to support ongoing studies to evaluate the ability of the NIOSH bioaerosol sampler to collect viable airborne viruses under various environmental conditions and efforts to devise techniques to preserve the viability of airborne viruses during collection. Improved and validated methods for viral aerosol sample collection using the NIOSH sampler will lead to joint applications of the sampler that will help bridge public health and environmental concerns. This project should result in peer reviewed journal articles that will provide scientific data regarding the mechanism of Influenza transmission. The knowledge gained from this study will address specific NIOSH research goals to reduce or eliminate transmission of infectious diseases in health care settings among workers in the health care and social assistance sector.

Project contact: Don Beezhold
Health Effects Laboratory Division, Allergy and Clinical Immunology Branch
(304) 285-6121
Project period: 2009-2013

Assessment of Engineered Materials on Respiratory Immunity (NTRC)

A preliminary study of biological effects of Single Walled Carbon Nanotubes (SWCNT) in vitro and in vivo revealed clear interaction between Engineered Nanomaterials (ENs) and immune cells affecting their primarily function. In particularly, it was found that SWCNT suppressed innate immunity associated with reduced recognition of the particles and bacteria by alveolar macrophages, suppressed ROS production and decreased bacterial clearance causing extended pulmonary inflammation, inpaired innate immunity and lung lesions. The results of these studies will benefit to hazard characterization and risk assessment of ENs with respect to immune outcomes, based on the following steps: a) analysis of the most important physico-chemical characteristics of the tested ENs influencing the response in vitro; b) extrapolation of in vitro results to the in vivo situations using appropriate scaling algorithms; c) extrapolation of the animal-based model systems to human exposures. Overall, the project objective is to perform a comprehensive assessment of adverse respiratory immune effects of selected ENs in order to understand how the benefits of the emerging nanotechnologies can be realized while minimizing potential risks to human health during manufacturing.

Project contact: Anna Shvedova
Health Effects Laboratory Division, Pathology and Physiology Research Branch
(304) 285-6121
Project period: 2009-2012

Immune and Inflammatory Aspects of Occupational Rhinitis

Workers with occupational asthma often have concurrent occupational rhinitis with the likelihood that rhinitis developed first. Thus, understanding the mechanisms of occupational rhinitis is an important area of research in occupational safety, health and medicine. A combined study design utilizing human and animal research will be employed to identify the orthologously conserved pathways and gene networks that characterize the pathobiology of occupational rhinitis induced by diisocyanates. The outcomes of this research will benefit occupational safety and health through improved diagnosis and prevention of allergic airways disease caused by diisocyanates. These studies directly relate to the mission of the NORA Services Sector, Construction Sector, Manufacturing Sector, Immune and Dermal Cross-sector and the Respiratory Diseases Cross-sector. The research outcomes will substantially contribute to achieving the goals identified in these NIOSH programs.

Project contact: Victor Johnson
Health Effects Laboratory Division, Toxicology and Molecular Biology Branch
(304) 285-6121
Project period: 2007-2010

Genetics in Occupational Diseases

This multi-year program is designed to investigate susceptibility gene variants that contribute to the development and severity of occupational ICD and asthma using high-density and high-throughput genotyping platforms. Previous and on-going studies in our laboratory showed that cytokine polymorphisms have a major influence on silicosis, dementia, accelerated decline in lung function and vaccine efficacy. Understanding the genetic contribution to the development, progression and outcomes of complex occupational diseases will help improve the accuracy of risk assessment and improve safe exposure levels for genetically susceptible groups in the workforce. This information could ultimately lead to the identification of novel therapeutic targets and preventative strategies for better management of work-related diseases.

Project contact: Berran Yucesoy
Health Effects Laboratory Division, Toxicology and Molecular Biology Branch
(304) 285-6121
Project period: 2007-2012

Immunotoxicity of Workplace Xenobiotics in Humans

The overall goal of this project is to study the immunological consequences of occupational chemical exposures. This IAG is a multi-task effort between NIOSH and the NIEHS/NTP. Efforts within this IAG include projects to identify and characterize immunotoxic agents, establish risk factors for clinical immunotoxicity, identify incidence of occupational immune mediated diseases, and establish improved methodology and biomarkers for their identification. The individual project will add to the immunological database that has been established for humans exposed to xenobiotics in the workplace. The need to expand this database and validate testing strategies has been recognized by expert panels and international organizations. This information would 1) further improve risk assessment strategies by providing data to determine if a correlation exists between rodent and human immunotoxicity data; 2) determine the types of responses and classes of chemicals which alter immune parameters to predict whether immunologic endpoints can be utilized as biomarkers of xenobiotic exposure; identify the genetic determinants that influence immunological/inflammatory disorders that can be influenced by occupational exposures and 3) determine if xenobiotic-exposed populations with altered immune function have a greater risk for the development of clinical disease. This project should result in peer reviewed journal articles which will provide scientific data regarding the immunotoxic effect of chemical exposures. The knowledge gained from this study will address specific NIOSH research goals for reducing respiratory disease and occupational skin disease and hazard identification of occupational chemicals/allergens.

Project contact: David Weissman
Division of Respiratory Disease Studies
(304) 285-5749
Project period: 2005-2011

 

 
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  • Page last reviewed: December 18, 2012
  • Page last updated: December 18, 2012
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